Ionic liquids (ILs) have been used as alternative solvents for a wide range of chemical processes. Over the past decade, while the “greenness” of ILs has been debated, the emergence of industrial processes which make use of ILs to improve their environmental profiles (West) continues to fuel the explosion in research focused on ILs. ILs are of industrial value in the “green” sense, as they possess favourable properties including very low volatility and facile separation of products in suitable cases. This means that ILs have very low vapour pressure and produce virtually no hazardous vapours when compared with traditional volatile solvents. ILs are also attractive as their properties may be tailored or fine-tuned to meet various needs, and ILs now have applications as solvents, chiral coordinating solvents and directing catalysts. ILs now also find uses in applications such as electrochemistry, for example, in wet cell batteries, and also in photochemistry and organic synthesis, as both solvents and as catalysts.
ILs based on aromatic heterocyclic cations, such as imidazolium and pyridinium cation-based ILs are particularly popular due to their ease of modification, low charge density about the aromatic ring and cation stability under acidic conditions. The low aromatic charge density, in particular, means it is easy to synthesize low melting salts (low melting point being a fundamental property of ILs). Unfortunately, traditional ILs based on N-alkylimidazolium and N-alkylpyridinium cores do not lend themselves to biodegradability. In fact, it is well known that dialkyl substituted imidazoles and unsubstituted N-alkylpyridinium rings have limited biodegradability. Biodegradability can be improved with fuctionalisation of the core sidechain(s). In particular, introduction of ester functionality into the IL is known to improve the overall biodegradability.
In 2002, Gathergood and Scammells designed environmentally friendly biodegradable achiral ILs, containing side-chains which act as potential sites of enzymatic hydrolysis. Subsequent studies by Gathergood, directed towards the development of biodegradable, low toxicity solvents that have performance advantages over established solvent media indicated that the presence of an ester linkage in the side chain of the IL cation promoted biodegradation. The IL counterion was also a significant factor, with octylsulfate examples proving readily biodegradable. The Gathergood group recently reported that key features which improve biodegradation and reduce antimicrobial toxicity were also required for improved catalyst performance in the selective hydrogenation of phenoxyocta-2,7-diene. Further investigations by Gathergood into changes in conversion and selectivity in the hydrogenation reactions of cinnamaldehydes and benzyl cinnamate using novel biodegradable and/or low toxicity ILs and recycling of the catalyst/IL media resulted in a communication being published in the journal Green Chemistry (Morrissey et al).
International Patent Application No. PCT/EP2008/060978 describes ionic liquid (IL) solvents for chemical synthesis based on an N-alkylimidazolium cation core which have enhanced biodegradability and reduced toxicity relative to existing imidazolium bases ILs such as 1-butyl-3-methylimidazolium (bmim) salts, many of which produce a score of over 60% biodegradability over 28 days in the Sturm Test, the Closed Bottle Test (OECD 301D) or the CO2 Headspace Test (ISO 14593).
Several groups have approached the problem of increasing biodegradability by developing biorenewable ILs based on cheap, readily available molecules from biological molecules that can be sourced from nature and recycled in known biochemical pathways (e.g. Han's choline cations combined with proline carboxylate anion). While these biorenewables are intended to take the place of synthetic quaternary nitrogen cations such as the alkylammonium, dialkylimidazolium and pyridinium components often found in previous generation ILs, it is sometimes the case that a biorenewable molecule, such as choline (derived from lipids and important as an acetate in neurotransmission) is more cheaply available via a synthetic process (choline is prepared commercially from ethylene oxide and trimethylamine via the Davy Process). Research has led to new ILs where cations are derived from alpha-amino acids and alpha-amino acid ester salts. Since amino acids are essentially a ‘food source’, they can be taken up by bacteria, fungi etc., into the usual biochemical pathways where they are degraded. These ILs are particularly advantageous compounds, since stereocentres have been retained in the final IL product (Chen et al).
However robust, imidazolium-based ILs, which are stable to a wide range of chemical environments (with notable exceptions) and can be accessed by short, simple synthetic routes, still dominate the field.
The special characteristic that chiral ionic liquids (CILs) possess of being tunable solvents, in which solvent interactions such as polarity, hydrophobicity, and π-π stacking interactions can be tailor-made to an application means that CILs are attracting considerable interest as chiral solvents (Baudequin et al) with many possible applications. Thus, chiral ionic liquids (CILs) are attracting much interest. Solvent chirality is achievable with complex solvents such as ILs. Chirality may be found in either or both of the IL cation and anion.
Although chiral solvents have been known for many years, their major application has been in NMR detection of enantiomeric excesses in chiral compounds. Since Seebach's landmark discovery of modest asymmetric with a chiral solvent in 1975, only a few examples of asymmetric induction using chiral solvents have appeared. Excessive cost, a paucity of applications and modest performance have limited their usefulness. In 2007, Hüttenhain achieved an optimum enantiomeric excess of only 59% in the reduction of acetophenone to 1-phenylethanol at −78° C. using BH3 together with ZnCl2 and (S)-methyl lactate as the solvent, together with a THF co-solvent.
Earle et al reported a first chiral IL solvent possessing chirality in the anion, comprising [bmim][lactate](bmim=butyl methyl imidazolium), having a chiral anion of (S)-configuration and its use in reaction of dienes and dienophiles. However the products of the reaction were not asymmetric. The [bmim][lactate] ionic liquid was synthesised by the reaction of sodium (S)-2-hydroxypropionate and [bmim]Cl in acetone. The resultant precipitate of sodium chloride was filtered off and the acetone evaporated.

Chinese Patent Application Publication No. 1 749 249 describes a chiral ionic liquid for use as a chiral catalyst and a chiral solvent, the ionic liquid comprising a cation and a chiral lactate anion.
N-alkylated methyl ephedrine has been used as a chiral cation for ILs in a Baylis-Hillman reaction and chirality was induced in the product. It was proposed that asymmetric induction resulted from the hydroxyl group of methyl ephedrine which could assemble the reagents into a highly ordered transition-state, favouring the desired configuration (Pegot et al).
United States Patent Publication No. US 2005/0065020 describes ionic liquids which have a secondary hydroxyl group and an atom efficient method for the preparation of these ionic liquids by opening an epoxide with an alkylimidazole in the presence of acid. This procedure leads directly to chiral ILs, where chirality is conferred on the cation. Preferably the ILs contain an N-(2-hydroxyalkyl) substituent to provide compounds of general formula (I*), wherein X represents an anion:

Howarth et al, described [N,N-di(2′S-2′-methylbutane) imidazolium bromide]. This imidazolium ion has two chiral side chains and was used in a catalytic Diels-Alder reaction. The products were produced in minimal enantiomeric excess only. Furthermore, this chiral IL is likely to be expensive to make in an optically enhanced form, since the synthesis requires an optically enhanced bromide compound or alternative alkylating agent in the synthesis.
United States Patent Publication No. US 2003/0149264 describes chiral ionic liquids of the general formula: [A]n+[Y]n−, whereby n=1 or 2 and the anion is an anion of an organic or inorganic proton acid and the cation is an optically active organic ammonium cation with up to 50 carbon atoms and at least one chiral centre and at least one functional group, whereby the functional group can produce a coordination by forming hydrogen bridges or providing free electron pairs and at least one chiral centre has a distance of up to 5 atomic bonds from the functional group. The ILs described herein may be used to separate racemates into individual enantiomers, as solvents for asymmetric inorganic and organic synthesis and also as solvents for asymmetric catalysis in organic and inorganic reactions. Typically the ILs find use as solvents for Diels-Alder reactions, benzoin reactions and asymmetric catalysis, in particular hydration and hydrovinylation.
More recently, tetra-n-hexyl-dimethylguanidinium (R)-mandelate, a chiral ionic liquid in which a mandelate anion is providing chirality, has been used as a solvent for asymmetric rhodium(II) carbenoid insertion by Alfonso.
In this reaction an α-phosphono-α-diazoacetate was cyclized via a C—H insertion reaction in the presence of Rh2(OAc)4 with a CIL solvent to give a γ-lactam in 72% yield, as a trans/cis mixture (67/33) and with 27% enantiomeric excess. However, undesirably, the IL may not be inert since the mandelate anion may potentially act as a nucleophile or base in many reactions.
Chiral ILs have also found use in the separation sciences. For example, United States Patent Publication No. US 2006/0025598 describes diionic liquid salts having a solid/liquid transition temperature of about 400° C. or less. The diionic liquid salt includes two monoionic groups separated by a bridging group and either two monoionic counter ions or at least one diionic counter ion. The diionic liquid salts may be immobilized as stationary phases for gas chromatography (GC). The IL stationary phases are said to be highly selective, stable and resistant to temperature degradation. In a preferred embodiment, the stationary phases are made from diionic species which are chiral and optically enhanced. In one embodiment the diion or the salt-forming species is chiral, with at least one stereogenic centre to provide racemic or optically enhanced mixtures.
U.S. patent application Ser. No. 11/177,093 describes optically enhanced chiral ionic liquids for gas chromatography and as a reaction solvent. Both optically enhanced chiral cationic and optically enhanced chiral anionic liquids are described. Optically enhanced chiral cations include (−)—N-benzyl-N-methylephedrinium NTf2, isoleucine-based ILs, menthol-substituted methyl imidazolium IL, (−)-cotinine OTf, 1-((R)-1,2-propanediol)-3-methylimidazolium chloride, and a (+)-chloromethyl methyl ether imidazolium IL salts, amongst others.
